Confocal imaging is probably the most advanced 3D imaging method that can be applied to living cells and used to visualize neuronal structure and function. As equipment becomes ever more sophisticated, the application of confocal microscopy has become increasingly common and productive. To increase efficiency, much work has been done on the confocal optical systems. However, there is only one component of a confocal system that can offer an order of magnitude improvement - the sensor. This proposal requests funding to develop a solid state sensor, the "CCDiode", that offers such a performance improvement. PixelVision, Inc., a leader in the manufacture of high performance CCDs and CCD cameras, teamed with Dr. James Pawley (U of Wisconsin, Madison), a leading con focal microscope researcher, propose to design and manufacture a nearly ideal, confocal CCD camera for neuroscience applications with greater than 90 percent quantum efficiency and better than 2 electrons noise. The CCDiode sensor will overcome the instability and low quantum efficiency associated with conventional photodiode approaches. In the Phase I effort, a pre-existing prototype CC Diode sensor will be integrated with imaging electronics and the prototype camera will be used to demonstrate the advantages of this innovative approach. The results of the Phase I tests, conducted in real biological applications, will be used to design an improved and optimized imager that will be manufactured in the Phase II effort. In the Phase II effort, the custom CCD fabrication will be completed along with an experimental design effort that will allow further improvements to be realized. Once optimized, the CCD will be integrated with the camera electronics and application specific software. The novel CCDiode confocal camera will be validated in a research environment, compared to conventional systems, demonstrated superior in performance to conventional photodiode approaches, and optimized for use in commercial markets. PROPOSED COMMERCIAL APPLICATIONS: There is increasing interest amongst confocal manufacturers to incorporate 3D deconvolution programs with their instruments (Avanash, 1995; Avanash and Malecki, 1996). The performance of the confocal/multi- photon approach will increase if the QE of the detector can be improved. Additionally, as studies usually require the living cell he illuminated with a laser beam, the cells are often injured. The CCDiode innovation will therefore dramatically increase the amount of data that can be achieved. PixelVision. Inc. is a leading supplier of instrumentation to the bio medical market and intends to aggressively pursue the commercialization of this innovation. All major confocal instrument manufacturers are aware of these developments and have expressed strong interest in the development of such a detector. The proposed Project Team has a long history of commercializing government funded imaging technologies.